The human T-cell population is composed of distinct subsets with unique functions. A delicate balance between effector and regulatory cells is required for immune homeostasis. Aberrations in immunoregulatory T-cell subsets have been shown to be central in a number of diseases (juvenile rheumatoid arthritis, acute graft vs host disease, acquired agammaglobulinemia, lupus erythematosus). Using monoclonal antibodies that identify T-helper (T4), T-suppressor (T5), and a common T cell (T3) antigen we have recently shown that patients with active multiple sclerosis (MS) have a selective decrease in T-suppressor cells in peripheral blood, that this aberration correlates with disease activity, and more importantly, is not seen in other neurologic diseases. We plan to characterize the immunologic consequences of this abnormality and its relationship to clinical disease by defining: 1) Immunologic classification of nervous system "autoimmune" diseases according to immunoregulatory T-cell function (optic neuritis, Guillain-Barre, subcategories of MS (e.g., relapsing remitting vs chronic progressive); 2) Temporal relationship of abnormalities of T-cell subsets to disease activity; 3) Effect of immunotherapeutic regimens on T cell subsets and function; 4) T cell phenotypes in the cerebrospinal fluid from MS patients in active disease and from controls; 5) Immunohistochemical studies of lymphocytic infiltrates in formalin fixed brain specimens from patients with acute MS to determine which lymphocyte subsets are present; 6) The relationship of lymphocytotoxic antibodies to altered T cell subsets and an investigation of shared and antigenic structures between the CNS and lymphocyte using T cell monoclonal antibodies and lymphocytotoxic antibodies from MS patients; and 7) In vitro studies of immunoregulation with functional studies of T-suppressor and T-helper function of MS lymphocytes on various parameters of immune reactivity (e.g., immunoglobulin production).